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Jonlyn Lippert
11/27/17
Final Draft
Quorum Sensing by Bonnie Bassler

Quorum Sensing
Bacteria, single cell organisms, talk through chemicals that allows them to do something interesting. It
lets them synchronize their movement and behavior. It lets them act as a multicellular organism. This is known
as Quorum sensing. They can easily affect plants and humans through this. Quorum sensing bacteria release
chemical signals called Autoinducers. Autoinducers increase cell density. Gram-positive plus Gram-negative
bacteria use quorum sensing as a way of doing many activities. Activities such as antibiotic production, biofilm
formation and bacteria grouping. Quorum sensing begins, with a low density population, by Autoinducers
diffusing through the cell and then attaches to the regulatory protein. The attached group then binds to the
cell's DNA. It then allows for the creation of new Autoinducers which then leave the cell, also through diffusion.
The process repeats until the bacteria density is extremely heavy allowing them to create a Biofilm. Quorum
sensing helps bacteria to express gene expression. Quorum sensing was discovered by Woody Hastings when
he discovered Vibrio harveyi were bioluminescent when the bacteria were densely populated!
Quorum sensing can be minimally broken down into a few steps. The first being a biochemical signal
molecules by the cell. Then the signals are released, by the cells, into the local environment. Then the
molecule cross a threshold, allowing them to be identified by certain receptors. Finally, the identification allows
for gene expression. Quorum sensing can differentiate between Gram-Negative and Gram-Positive
bacteria.Quorum sensing, or the control of gene expression in response to cell density, is used by both Gram-
negative and Gram-positive bacteria to regulate a variety of physiological functions. In all cases, quorum
sensing involves the production and detection of extracellular signalling molecules called autoinducers[1].
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In Gram-Negative bacteria, Quorum sensing begins is a Lux type

Quorum. Lux responds to the production and response to the acylhomoserine
lactone signaling (AHL). Lux type Quorums are made up two things. One being a
transcriptional regulators. Transcriptional regulators are proteins that bind to a
certain DNA sequence. The transcriptional regulators for Lux type Quorum is
LuxR. The second part to Lux type Quorums are autoinducer synthase. LuxL, an
autoinducer synthase, synthesizes AHL from adenosylmethionine. AHL can
freely across membranes, due to its tiny size. When the population rises and
becomes more dense, AHL can join LuxR to the cytoplasm of the cell. In a
Gram-Negative bacteria, like Vibrio fischeri , can cause bioluminescence. This is done by the transcriptional
regulator, LuxR !
Theres another Gram-Negative bacteria that produces a different signal. The bacteria, Pseudomonas
aeruginosa, produces 2-heptyl-3-hydroxy-4-quinolone [2.]. It has control over the signal LasB, which is LasB
elastase. It also has two Quorum sensing systems, Las and Rhl. Which both work because of autoinducers N-
L-homoserine lactone plus N-butyryl. P. aeruginosa multiplies greatly due to the signal molecules bind to
transcriptional activator proteins [3 & 4.] They also activate the transcriptional activator proteins. The Rhl
system also modifies the expression of genes controlled by the Las system. This helps P. aeruginosa to grow
as a biofilm for cystic fibrosis of the hosts lungs.A biofilm is an assemblage of surface-associated microbial
cells that is enclosed in an extracellular polymeric substance matrix [9]. It helps to protect the bacteria from
the hosts immune system. The formation of biofilms is controlled by the Las system. LasL is mutated to form a
smooth, flat biofilm [8.]. Biofilms can be found and produced by Gram-Negative bacteria and Gram-Positive
bacteria.
In Gram-Positive bacteria things are a little different. Rather than AHL or other signaling molecules,
they use oligopeptides also called autoinducing peptides (AIPs)[6]. Oligopeptides can consist of two to twenty
amino acids held together by peptide bonds. Its secreted by an ATP transporter. When Cell population rises,
AIP numbers increase. The AIP signals are then detected by sensor kinases. This results in a phosphorylation
of a regulatory protein.
One interesting Gram-Positive bacteria is
Streptococcus. In 1931, that genetic transformation was
discovered. The accesoritory gene (AGR) is found in
Streptococcus. The five genes that has been discovered in the
regulatory system. The signal that developed is called
Competence stimulating peptide (CSP). The CSP is seventeen
amino-acids long. ATP bound transporter of ComAB secretes
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peptides outside of the cell. ComD is a kinase protein that discovers CSP. It phosphorylates ComD
transferring the phosphoryl group to the regulator ComE. The newly phosphorylated regulator ComE activates
the transcription of ComX. ComX is the factor required for the transcription of any structural genes in
Streptococcus!
Therefore one can expect unidentified regulators responsible for transiting Streptococcus
pneumonia out of the competence state. The remarkable competence property of Streptococcus
pneumonia is its capability to take a foreign DNA irrespective of its sequence and the species of
origin[7].
The ability for bacteria to evolve to areas of high cell density is needed for survival and reproduction.
Speakers Labs Contributions
Bonnie Bassler, the princeton lecturer, provided a wide range of knowledge in her lecture. She
explained the bioluminescence of the Hawaiian bobtailed squid. Bassler shows use two organs which are filled
with bacteria that form a symbiotic with the squid.They get nutrients from the squid and squid gets lights to help
hide it while it hunts. The organs are filled with millions of Vibrio fischeri. Theres no know information on how
the squid hosts this amount of V.fischeri. They product an autoinducer that tells them that since theyre inside
that they should produce light[14].
She then provides a list of bacterias that contain LuxS genes and make autoinducer two. This is a list of
clinical pathogens. She then discusses the possibilities of making an anti-Quorum. Biologists are now trying to
create antibiotics that stops that the communication between the bacteria rather than killing the bacteria. This
is so they cant count each other and turn on virulence. The list contains Gram-Negative and Gram-Positive
bacteria. Its believe that autoinducer two is older than the split between Gram-Negative and Gram-
Positive[14].
Bassler also explains what LuxS does and how autoinducer two is made. It begins with S-adenosyl-. L-
methionine (SAM) utilization. Methionine is converted into S-adenosylmethionine by MetK. Sam does what it
does and puts a methyl group on substrate. Dna or Rna gets what its wants but with a byproduct called S-
adenosylhomocysteine (SAH),which is toxic. Cells decrease toxicity by an enzyme called pfs. It takes adenine
away from SAH and creates S-ribosyl homocysteine (SRH). Due to an unknown enzyme SRH gets converted
into homocysteine. LuxS carries out the last step as it was the unknown enzyme. The process creates
autoinducer two [14].
Quorum sensing plays an interesting role in medicine. P.aeruginosa, even with the use of antibiotics,
can still survive and live in a cystic fibrosis lung. They do this by using Quorum sensing
to create a biofilm, previously mentioned before. They produce two Quorum signals.
however, the relative abundance of these signals was opposite to that of the
standard P. aeruginosa strain PAO1 in laboratory broth culture... When we grew these
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isolates and PAO1 in a laboratory biofilm model, the signal ratios were like those in cystic fibrosis sputum. Our
data support the hypothesis that P. aeruginosa are in a biofilm in cystic fibrosis sputum[10].
Specific P. aeruginosa strains, with Quorum sensing, can help identify things that interrupt with Biofilm
Formation. They serve as Biomarkers for this purpose.
It can also be used in Pharmaceuticals. It can be used to develop antimicrobial therapy. The
autoinducer (AI-2) is a signaling molecule. LuxS can code the AI-2. This can be found in bacteria such as
Helicobacter, Neisseria, or Porphyromonas. AI-2 is needed by most bacteria for to be contagious. For some
bacteria the AI-2 signal isnt needed for virulence. It can be a metabolic byproduct and be used as a drug
target. Due to this, anti-biofilm and anti-Quorum sensing medicine has been developed or currently developing.
Many tactics at interrupting Quorum sensing can be used like stopping of the AHL signal reception[11].
Quorum blockers can act as a suppressor but doesnt kill the bacteria. Staphylococcis Quorum sensing
system is Arg and is made of the gene ArgA, ArgB, ArgC, and ArgD. Derivatives...inhibit the agr system
response and efficiently block the development of S. aureusinduced lesions in mice. These derivatives have
been proposed as quorum-sensing blockers for the treatment of staphylococcal infection [12].
Pharmaceuticals companies are targeting parts of Quorum sensing to help fight antibiotic resistance.
One targets are receptors.Quorum receptors are AHLs, AIPs and AI-2s. Another target are disruptions by
plants and other bacteria [13]. The marine red alga D. pulchra secretes halogenated furanones and enones
that structurally resemble the AHL autoinducer of Serratia liquefaciens, antagonize the binding of AHLs at the
receptor, and successfully ward off infestation of S. liquefaciens[13]. Ligands can also be used to disrupt
Quorum sensing. Ligands interact with Quorum receptors in a concentration-dependent manner. However
Ligase interrupts the Quorum signals from the receptors. Such receptors being LuxR, Luxl, the AIP receptor,
LuxS. In Gram-Negative bacteria, it interrupts at the Lux binding sites. In Gram-Positive bacteria, it interrupts
the AIP processing [13].
Quorum sensing is a form of communication between bacteria and allows them to act as a multicellular
organism. It can differentiate between Gram-Negative, which uses a Lux-type system, and Gram-Positive,
which uses an autoinducer peptide system. Both systems move through a threshold of low density to that of
high density. The higher the density, the more autoinducers made, which allows for more Quorum sensing.
Quorum sensing can cause many things. It can cause bioluminescence, which humorously enough, is how
Quorum sensing was discovered! It can also help a bacterias virulence, and to create biofilms in Cystic
Fibrosis.
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Citations
1. Bassler, B L. How Bacteria Talk to Each Other: Regulation of Gene Expression by Quorum Sensing. Current
Opinion in Microbiology., U.S. National Library of Medicine, Dec. 1999,
www.ncbi.nlm.nih.gov/pubmed/10607620.
2. Miller, M B, and B L Bassler. Quorum Sensing in Bacteria. Annual Review of Microbiology., U.S. National
Library of Medicine, www.ncbi.nlm.nih.gov/pubmed/11544353.
3. Pesci, E C, et al. Quinolone Signaling in the Cell-to-Cell Communication System of Pseudomonas Aeruginosa.
Proceedings of the National Academy of Sciences of the United States of America., U.S. National Library of
Medicine, 28 Sept. 1999, www.ncbi.nlm.nih.gov/pubmed/10500159.
4. Pesci, Everett C. Quinolone Signaling in the Cell-to-Cell Communication System of Pseudomonasaeruginosa.
Quinolone Signaling in the Cell-to-Cell Communication System of Pseudomonasaeruginosa, 28 Sept. 1999,
www.pnas.org/content/96/20/11229.long.
5. Quorum Sensing in Bacteria. Quorum Sensing in Bacteria | Annual Review of Microbiology,
www.annualreviews.org/doi/abs/10.1146/annurev.micro.55.1.165?journalCode=micro.
6. Sifri, Costi D. Quorum Sensing: Bacteria Talk Sense | Clinical Infectious Diseases | Oxford Academic. OUP
Academic, Oxford University Press, 15 Oct. 2008, academic.oup.com/cid/article/47/8/1070/345306.
7. Vijayalakshmi, M. Quorum Sensing in Gram-Negative and Gram-Positive Bacterial Systems. Quorum Sensing
in Gram-Negative and Gram-Positive Bacterial Systems, pp. 110.
8. Hentzer, Morten. Inhibition of Quorum Sensing in Pseudomonas Aeruginosa Biofilm Bacteria by a Halogenated
Furanone Compound. Http://Www.microbiologyresearch.org,
www.microbiologyresearch.org/docserver/fulltext/micro/148/1/1480087a.pdf?expires=1512054039&id=id&accna
me=guest&checksum=6370ED3386D33E8D79347DCE032074E1.
9. Donlan, Rodney M. Biofilms: Microbial Life on Surfaces. Emerging Infectious Diseases, Centers for Disease
Control and Prevention, Sept. 2002, www.ncbi.nlm.nih.gov/pmc/articles/PMC2732559/.
10. Singh, Pradeep K., et al. Quorum-Sensing Signals Indicate That Cystic Fibrosis Lungs Are Infected with
Bacterial Biofilms. Nature News, Nature Publishing Group, 12 Oct. 2000, www.nature.com/articles/35037627.
11. Hentzer, Morten, and Michael Givskov. Pharmacological Inhibition of Quorum Sensing for the Treatment of
Chronic Bacterial Infections. Journal of Clinical Investigation, American Society for Clinical Investigation, 1 Nov.
2003, www.ncbi.nlm.nih.gov/pmc/articles/PMC228474/.
12. Vuong, Cuong, et al. Impact of the Agr Quorum-Sensing System on Adherence to Polystyrene in
Staphylococcus Aureus | The Journal of Infectious Diseases | Oxford Academic. OUP Academic, Oxford
University Press, 1 Dec. 2000, academic.oup.com/jid/article/182/6/1688/914441.
13. Raffa, Robert B., et al. Bacterial Communication (. Journal of Pharmacology and Experimental Therapeutics,
American Society for Pharmacology and Experimental Therapeutics, 1 Feb. 2005,
jpet.aspetjournals.org/content/312/2/417.short.
14. ibioseminars. Bonnie Bassler (Princeton) Part 1: Bacterial Communication via Quorum Sensing. YouTube,
YouTube, 27 Mar. 2010, www.youtube.com/watch?v=saWSxLU0ME8.